crossing96/oncoscreening huggingface dataset:
Different immunohistochemical and ultrastructural phenotypes of squamous differentiation in bladder cancer.	Besides worse prognosis of bladder cancer with squamous differentiation (pure squamous cell carcinoma (SCC) or mixed urothelial carcinoma (UC/SCC)), high-grade non-keratinising squamous differentiation is difficult to identify in haematoxylin-eosin stainings. This study aims to validate routine immunohistochemical markers for squamous differentiation in a larger cohort of patients. Tissue microarrays of 89 pure SCCs and mixed UC/SCCs, 66 urothelial carcinomas (UC), precursor lesions and normal urothelium were stained for cytokeratin (CK) 5/6, CK 5/14, CK 7, CK 20 and uroplakin III. Electron microscopy was performed to confirm the differentiation. Pure SCCs displayed staining throughout the epithelium for CK 5/6 (76.6% (36/47)) and CK 5/14 (95.8% (46/48)), focal staining for CK 7 (28.9% (13/45)) and no staining for CK 20 and uroplakin III (both 0% (0/48)). UCs exhibited a basal or diffuse staining for CK 5/6 (30.2% (16/53)) and CK 5/14 (57.1% (32/56)), focal positivity for CK 7 (83.6% (46/55)), CK 20 (50.9% (29/57)) and uroplakin III (21.8% (12/55)). Each marker discriminated SCC and UC significantly (p < 0.01). A third subgroup rarely showed full epithelial staining for CK 5/6 (14.3% (1/7)) and CK 5/14 (28.6% (2/7)), focal staining for CK 7 (85.7% (6/7)) and no staining for CK 20 and uroplakin III (both 0% (0/7)). Electron microscopy could prove both, SCC and UC characteristics, revealing a transient type. A staining pattern with CK 5/6- and CK 5/14-positivity plus CK 20- and uroplakin III-negativity identified squamous differentiation in bladder tumours and revealed a third type of squamous transdifferentiation.	bladder
Differential miRNA expression profiles in bladder urothelial carcinomas.	The urothelial carcinoma is the most common pathological type of bladder tumor. Creation of lists of miRNAs differentially expressed between this tumor type and normal tissue might help identify new diagnostic and prognostic markers. We therefore performed the present miRNA microarray analysis with 25 cases of bladder urothelial carcinomas and adjacent normal bladder tissue. The results showed a panel of 51 differentially expressed miRNAs with at least 2-fold differences in expression compared with the normal controls, including 20 up-regulated and 31 down-regulated examples. The expression levels of ten of the top dysregulated miRNAs, mir-1, mir-145, mir-143, mir-100, mir-200b, mir-708, mir-133a, mir-133b, mir-125b and mir-99 were experimentally verified using real-time RT-PCR analysis. These findings suggest that these miRNAs may be involved in bladder urothelial carcinoma pathogenesis and have potential as biomarkers.	bladder
Knockdown of ribonuclease inhibitor expression with siRNA in non-invasive bladder cancer cell line BIU-87 promotes growth and metastasis potentials.	Human ribonuclease inhibitor (RI) is a cytoplasmic acidic protein. RI is constructed almost entirely of leucine-rich repeats, which might be involved in some unknown biological functions like other structurally similar proteins besides inhibiting RNase A and angiogenin activities. Our previous experiments demonstrated that up-regulating RI might effectively inhibit some tumor growth and metastasis. However, the down-regulating RI influence on the tumor does not have any report until now, the mechanisms underlying antitumor of RI have not been fully understood. In this study, the efficient RNA interferences of RI were constructed using a plasmid vector and identified with RT-PCR, Western blot and Immunocytochemistry, then were transfected into non-invasive bladder cancer BIU-87 cells. We demonstrated that knockdown RI expression in BIU-87 cells could obviously change the cell morphology, rearrange the microfilaments and extend the lamellipodia, as well as enhance proliferation, increase migration, invasion and matrix metalloprotease level, and also reduce adhesion in vitro. BALB/C nude mice that were injected with the BIU-87 cells transfected RI siRNA showed a significant facilitation of the tumor with heavier tumor weight, higher density of microvessels, lower nm23-H1 and E-Cadherin expressions than those in the control group. Taken together, these experiments suggest that knockdown of RI could promote growth and metastasis potentials of BIU-87 cells. Our present findings reveal the novel mechanism that anti-tumor effect of RI is also involved in suppressing growth and metastasis, besides antiangiogenesis. The results show that RI may be a therapeutic target protein for bladder cancer and may be of biological importance.	bladder
DNA adducts of ortho-toluidine in human bladder.	BACKGROUND: 4-Aminobiphenyl (4-ABP) and o-toluidine are known human bladder carcinogens, but only 4-ABP-releasing DNA adducts are known. METHODS: Determination of 4-ABP and o-toluidine-releasing DNA adducts in epithelial and submucosal bladder tissues of sudden death victims (SDV: n=46), and bladder tumours (n=12) by gas chromatography/mass spectrometry. RESULTS: Above background, 4 and 11 of 12 tumour samples contained adducts of 4-ABP (0.057 ± 0.125 fmol/µg DNA) and o-toluidine (8.72 ± 4.49 fmol/µg DNA), respectively. Lower adduct levels were present in both epithelial and submucosal bladder tissues of SDV (4-ABP: 0.011 ± 0.022 and 0.019 ± 0.047 fmol/µg DNA; o-toluidine: 0.24 ± 0.63 and 0.27 ± 0.70 fmol/µg DNA). CONCLUSION: Detection of o-toluidine-releasing DNA adducts support the carcinogenicity of o-toluidine in the human bladder.	bladder
Expression of genes related to apoptosis, cell cycle and signaling pathways are independent of TP53 status in urinary bladder cancer cells.	Urinary bladder cancer is the fourth most common malignancy in the Western world. Transitional cell carcinoma (TCC) is the most common subtype, accounting for about 90% of all bladder cancers. The TP53 gene plays an essential role in the regulation of the cell cycle and apoptosis and therefore contributes to cellular transformation and malignancy; however, little is known about the differential gene expression patterns in human tumors that present with the wild-type or mutated TP53 gene. Therefore, because gene profiling can provide new insights into the molecular biology of bladder cancer, the present study aimed to compare the molecular profiles of bladder cancer cell lines with different TP53 alleles, including the wild type (RT4) and two mutants (5637, with mutations in codons 280 and 72; and T24, a TP53 allele encoding an in-frame deletion of tyrosine 126). Unsupervised hierarchical clustering and gene networks were constructed based on data generated by cDNA microarrays using mRNA from the three cell lines. Differentially expressed genes related to the cell cycle, cell division, cell death, and cell proliferation were observed in the three cell lines. However, the cDNA microarray data did not cluster cell lines based on their TP53 allele. The gene profiles of the RT4 cells were more similar to those of T24 than to those of the 5637 cells. While the deregulation of both the cell cycle and the apoptotic pathways was particularly related to TCC, these alterations were not associated with the TP53 status.	bladder
Prognostic significance of fluorescent in situ hybridisation in the follow-up of non-muscle-invasive bladder cancer.	AIM: To evaluate the potential contribution of a fluorescent in situ hybridization (FISH) as prognostic indicator of the risk of recurrence or progression in patients undergoing follow-up for non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: A total of 126 consecutive patients with a history of NMIBC being followed-up with urinary cytology and cystoscopy at a referral centre were studied. Patients with carcinoma in situ, or tumour stage higher than pT1 were excluded. A UroVysion FISH kit was used to detect four chromosomal abnormalities, specifically, locus 9p21, Ch 3, 7, and 17. Three FISH patterns were defined: negative; low-risk positive, i.e. positive staining for 9p21 and/or Ch3 abnormalities; and high-risk positive, i.e. positive staining for Ch7 and/or 17. RESULTS: Overall 73 out of 126 patients (57.9%) had a positive urinary FISH test. After a median time of 14 months, 46 FISH-positive patients underwent recurrence (36.5%) and in 15 patients there was progression of disease (11.9%). Among positive patients, the low-risk category was found in 34, and the high-risk in 39. Low-risk FISH-positive patients had a higher rate of recurrence as compared to FISH-negative patients, with a hazard ratio (HR) of 1.6. The recurrence rate was even greater in patients with a high-risk positive test, with an HR of 1.9. The limitation of the study was that the impact of intravesical treatment was not assessed. CONCLUSION: The urinary FISH test can be used as an aid in predicting the risk of recurrence during follow-up of patients with history of NMIBC.	bladder
RNA interference-mediated silencing of Foxo3 in antigen-presenting cells as a strategy for the enhancement of DNA vaccine potency.	The transcription factor Forkhead box O3 (Foxo3) has a critical role in suppressing the expansion of antigen-specific effector T-cell populations; hence, Foxo3 is a potential target for enhancing the antitumor immunity of cancer vaccines. In this report, we evaluated the potential of RNA interference (RNAi)-mediated silencing of Foxo3 in antigen-presenting cells as an adjuvant for HER2/neu DNA cancer vaccines. Bicistronic plasmids expressing the N-terminal extracellular domain of human HER-2/neu and the Foxo3 short hairpin RNA (hN'-neu-Foxo3 shRNA) or the scrambled control (hN'-neu-scramble shRNA) were subcutaneously injected into mice by gene gun administration to elicit antitumor immunity against p185neu-overexpressing MBT-2 bladder tumor cells. We found that mice treated with hN'-neu-Foxo3 shRNA showed greater reductions in tumor growth and longer survival times than mice treated with hN'-neu-scramble shRNA, indicating that the silencing of Foxo3 enhanced the antitumor efficacy of the HER-2/neu cancer vaccine. Cytotoxicity analyses further revealed that the Foxo3 shRNA-enhanced antitumor effect was associated with significant increases in the number of functional CD8(+) T cells and in the levels of cytotoxic T lymphocytes activity. Interleukin-6 was induced by hN'-neu-Foxo3 shRNA treatment but did not have a critical role in the antitumor effect of the hN'-neu-Foxo3 shRNA vaccine. Moreover, in vivo lymphocyte depletion analyses confirmed that the antitumor efficacy of the hN'-neu-Foxo3 shRNA vaccine depended on functional CD8(+) T cells. Finally, Foxo3 suppression was shown to markedly improve the effect of the HER-2/neu DNA vaccine in limiting the growth and lung metastases of MBT-2 cells. Overall, these results support RNAi-mediated silencing of Foxo3 as an effective strategy to enhance the therapeutic antitumor effect of HER-2/neu DNA vaccines against p185neu-positive tumors.	bladder
Bilharzial vs non-bilharzial related bladder cancer: pathological characteristics and value of cyclooxygenase-2 expression.	OBJECTIVE: • To assess the expression pattern of cyclooxygenase-2 (COX-2) in bilharzial and non-bilharzial related bladder cancer (BBC and NBBC) and its association with clinical outcome after radical cystectomy (RC). We also determined the clinico-pathological differences between BBC and NBBC. PATIENTS AND METHODS: • Immunohistochemical (IHC) staining for COX-2 was performed on archival bladder specimens from 315 patients treated with RC between 1997 and 2003. • Patients were divided into 2 groups: Group 1 comprised 205 patients (65%) with BBC and group 2 comprised 110 patients (35%) with NBBC. • Clinico-pathological differences were compared and altered IHC expression of COX-2 was correlated with clinical outcome in both groups. RESULTS: • The study included 315 patients (239 males and 76 females) with median age 54 y (range 31-79) and median follow up of 63.2 months after RC. • There was significant difference in histological types, tumor stage, grade, and architecture and COX-2 alterations between both groups (P < 0.05). • BBC presented with lower grade, higher stage, and non-papillary non-urothelial carcinoma. COX-2 overexpression was associated with pathological T stage (P= 0.01), grade (P < 0.001) and lymphovascular invasion (LVI) (P= 0.041). • COX-2 expression was an independent predictor of disease recurrence (HR 1.9, CI 0.99-3.626 and P= 0.05) and cancer specific mortality (HR 2.8, CI 1.155-6.73 and P= 0.023) only in BBC but not in NBBC (HR 1.6, CI 0.598-4.364, P= 0.344 and HR 0.349, CI 0.076-1.595, P= 0.175, respectively). CONCLUSIONS: • BBC differs pathologically and biologically from NBBC. BBCs present more frequently as low-grade, high stage non-papillary and non-urothelial cancers. BBCs with COX-2 alterations are associated with worse outcome after RC. • Our findings support the need for further evaluation of COX-2 and inflammatory signaling pathways as well as COX-2-targeted prevention and therapies in BC.	bladder
[Transvaginal repair of neobladder vaginal fistula].	INTRODUCTION: Neobladder vaginal fistula is a known complication after cystectomy and orthotopic neobladder in women. The exact incidence is still unknown, even if in some of the largest series is reported in about 5% of female patients. We present our personal experience with a case of neobladder vaginal fistula. METHODS: A fifty-year old woman affected by T2G3 bladder cancer underwent radical cystectomy and orthotopic neobladder in December 2007. Definitive pathological examination revealed pT3aN0G3 urothelial cancer with squamous aspects. Two cycles of neoadjuvant chemotherapy were administered before cystectomy. Three weeks after cystectomy, a retrograde cystography revealed a fistula between vagina and neobladder. At first, the patient was treated conservatively, keeping the urethral catheter for two months. Cystographies, repeated every month, recorded a reduction in size of the fistula but not the complete closure. A surgical correction was planned. Preoperative cystoscopy showed the neobladder opening of the fistula on the posterior wall. Then a transvaginal approach with fistula excision and a two layer cross suture were performed. RESULTS: At the cystography performed 1 month after surgical repair no fistula was detected, and the patient was completely dry. At 3 months follow-up the patient was completely dry. CONCLUSION: The development of a neobladder-vaginal fistula is a significant, even if infrequent, complication after cystectomy. In our case, we performed a transvaginal approach without tissue interposition, with good results. Such procedure is easy and effective and, in our opinion, can be tempted as first line surgical treatment.	bladder
Early detection of urothelial premalignant lesions using hexaminolevulinate fluorescence cystoscopy in high risk patients.	BACKGROUND: To evaluate fluorescence cystoscopy with hexaminolevulinate (HAL) in the early detection of dysplasia (DYS) and carcinoma in situ (CIS) in select high risk patients. METHODS: We selected 30 consecutive bladder cancer patients at high risk for progression. After endoscopic resection, all patients received (a) induction BCG schedule when needed, and (b) white light and fluorescence cystoscopy after 3 months. HAL at doses of 85 mg (GE Healthcare, Buckinghamshire, United Kingdom) dissolved in 50 ml of solvent to obtain an 8 mmol/L solution was instilled intravesically with a 12 Fr catheter into an empty bladder and left for 90 minutes. The solution was freshly prepared immediately before instillation. Cystoscopy was performed within 120 minutes of bladder emptying. Standard and fluorescence cystoscopy was performed using a double light system (Combilight PDD light source 5133, Wolf, Germany) which allowed an inspection under both white and blue light. RESULTS: The overall incidence was 43.3% dysplasia, 23.3% CIS, and 13.3% superficial transitional cell cancer. In 21 patients, HAL cystoscopy was positive with one or more fluorescent flat lesions. Of the positive cases, there were 4 CIS, 10 DYS, 2 association of CIS and DYS, 4 well-differentiated non-infiltrating bladder cancers, and 1 chronic cystitis. In 9 patients with negative HAL results, random biopsies showed 1 CIS and 1 DYS. HAL cystoscopy showed 90.1% sensitivity and 87.5% specificity with 95.2% positive predictive value and 77.8% negative predictive value. CONCLUSION: Photodynamic diagnosis should be considered a very important tool in the diagnosis of potentially evolving flat lesions on the bladder mucosa such as DYS and CIS. Moreover, detection of dysplasic lesions that are considered precursors of CIS may play an important role in preventing disease progression. In our opinion, HAL cystoscopy should be recommended in the early follow-up of high risk patients.	bladder
Clusterin immunoreactivity as a predictive factor for progression of non-muscle-invasive bladder carcinoma.	INTRODUCTION: There is a need for prognostic markers which can predict the subset of patients who will not respond sufficiently to conservative management in non-muscle-invasive bladder carcinoma. We analyzed the association of clusterin (CLU) with clinicopathological factors. MATERIALS AND METHODS: Immunohistochemical CLU expression was investigated in paraffin-embedded archival tissues of initial transurethral resection specimens of 46 patients with non-muscle-invasive bladder carcinoma. The result was expressed as the proportion of the number of CLU-containing tumor cells to the total number of tumor cells detected in each slide and 'percent CLU expression' was calculated for each patient. RESULTS: Of the 46 cases (35 male, 11 female), 18 were ≥ 65 years of age. CLU expression was significantly higher in male and elderly patients. Following the initial transurethral resection, 39 patients showed tumor recurrence, and progression was seen in 25 patients, of whom 17 progressed to muscle invasion during follow-up. Although there was no significant correlation between CLU expression and recurrence, significant correlation with overall progression and progression to muscle-invasive disease was observed in this cohort of patients (p = 0.001 and p = 0.014, respectively). Among the patients with progression to muscle invasion, 13 underwent radical cystectomy with pT2 tumor in 5 patients in the final pathology of surgical specimens and pT3 and higher in the remainder. CONCLUSIONS: CLU immunoreactivity showed correlation with age, gender and progression, mainly progression to muscle invasion. Thus, CLU can be used as a molecular marker to predict the potential of progression to muscle-invasive disease in a particular tumor which in turn may prove useful in the decision-making process for early cystectomy without losing time with conservative management.	bladder
Risk group stratification to predict recurrence after transurethral resection in Japanese patients with stage Ta and T1 bladder tumours: validation study on the European Association of Urology guidelines.	OBJECTIVE: • To validate the European Association of Urology (EAU) guidelines on risk group stratification to predict recurrence in Japanese patients with stage Ta and T1 bladder tumours. PATIENTS AND METHODS: • A cohort of 592 Japanese patients who were treated with transurethral resection (TUR) and histopathologically diagnosed with Ta and T1 urothelial carcinoma of the bladder were enrolled in this retrospective study. • The primary endpoint of the present study was recurrence-free survival, and the median follow-up duration was 37 months in recurrence-free survivors. RESULTS: • Multivariate Cox proportional hazards regression analysis showed that the Eastern Cooperative Oncology Group performance status (ECOG PS), prior recurrence rate, number of tumours and T category were independent predictors of time to recurrence (P < 0.05). According to the EAU guidelines for predicting recurrence, the vast majority of Japanese patients were classified into intermediate risk. • The intermediate-risk patients were further divided into intermediate-low-risk and intermediate-high-risk subgroups based on the European Organization for Research and Treatment of Cancer risk table, and a significant difference in the recurrence-free survival rates was found between these subgroups (P < 0.001). • It was also found that patients with high risk combined with intermediate-high risk had significantly poorer recurrence-free survival rates than those with low risk combined with intermediate-low risk (P < 0.001). CONCLUSIONS: • This is the first report on the ECOG PS as a potentially useful predictor for bladder tumour recurrence. • The risk group stratification of the EAU guidelines for recurrence might not be applicable to Japanese patients with Ta and T1 bladder tumours, but the subgroup classification of intermediate risk could be appropriate.	bladder
Genetic variations on chromosomes 5p15 and 15q25 and bladder cancer risk: findings from the Los Angeles-Shanghai bladder case-control study.	Genome-wide association studies have associated common variations at chromosomes 5p15 and 15q25 with lung cancer risk. The 5p15 locus has also been associated with increased bladder cancer risk in a recent report. The 15q25 locus has been associated with nicotine dependence and self-reported number of cigarettes smoked per day in some studies and it was proposed that its association with lung cancer may be mediated through differences in smoking behavior. Here, we investigated the roles of variations at 5p15 (rs401681, rs402710, rs2736098 and rs2736100) and 15q25 (rs1051730 and rs8034191) in bladder cancer etiology in two case-control studies conducted separately in Los Angeles County, CA, USA (498 cases and 588 controls) and in Shanghai, China (506 cases and 530 controls). We replicated the association between the 5p15 locus and bladder cancer among non-Hispanic whites (NHW) in Los Angeles [for rs2736100, per C allele odds ratio (OR) = 1.23; 95% confidence interval (CI), 1.02-1.48; P = 0.029] and among Chinese in Shanghai (OR = 1.22; 95% CI, 1.02-1.47; P = 0.033). Both rs1051730 and rs8034191 at 15q25 were rare among Chinese. Among NHW, a significant association was found between rs8034191 and bladder cancer which persisted after adjustment for cigarette smoking status, number of cigarettes smoked per day and number of years of smoking (per C allele OR = 1.26; 95% CI, 1.04-1.54; P = 0.017). Our results support 5p15 and 15q25 as susceptibility regions for bladder cancer risk.	bladder